TY - JOUR T1 - Experience-induced forgetting by WT1 enables learning of sequential tasks JF - bioRxiv DO - 10.1101/101360 SP - 101360 AU - Chiara Mariottini AU - Leonardo Munari AU - Ellen Gunzel AU - Joseph M. Seco AU - Nikos Tzavaras AU - Jens Hansen AU - Sarah A. Stern AU - Virginia Gao AU - Georgia E. Hodes AU - Scott J. Russo AU - Vicki Huff AU - Marc Birtwistle AU - Cristina M. Alberini AU - Robert D. Blitzer AU - Ravi Iyengar Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/03/17/101360.abstract N2 - Remembering and forgetting are important aspects of normal behavioral adaptation; however, the molecular basis of forgetting has been less studied. Using rat and mouse models we find that WT1, a transcriptional repressor that is activated in the hippocampus by LTP producing stimuli and behavioral memory, enables forgetting. Acute or tonic knockdown of WT1 did not affect short-term memory but enhanced long-term memory and enables a switch from circuit to cellular computation in the hippocampus. A control theory model predicts that WT1 could be a general repressor of memory or a regulator that preserves the ability to remember multiple sequential experiences. Using sequential training for two tasks, mice with non-functional WT1 have better memory for the first task, but show impaired memory for the second task. Taken together, our observations indicate that WT1 mediates an experience-activated forgetting process that preserves the capability of the animal to remember other new experiences.One sentence summary The transcription factor WT1 is a core component of an active forgetting process, and is required for normal behavioral flexibility by allowing LTM for successive experiences. ER -